Project Summary/Abstract Many patients suffer from conductive hearing loss (CHL) that is intractable to treatment, although their neurosensory system is intact. Round-window (RW) and bone-conduction (BC) stimulation have been proven to provide improved hearing for CHL that have failed various treatments. However these alternative stimulation methods have limited success. Their application is hindered both by a lack of knowledge of the unique mechanisms by which sound is transmitted to the cochlear partition by these stimulus methods, and limitations in the manner in which they are applied. Fresh human cadaveric preparations allow for controlled invasive experiments to elucidate these mechanisms, simulate various conductive diseases and evaluate and improve devices and treatments. With our new technique of intracochlear pressure measurement, we can better understand the mechanisms of these alternative sound stimulus pathways that differ substantially from normal air-conducted sound stimulation. Furthermore, the determination of the differential pressure stimulus, DP, allows monitoring of the input to the cochlea during normal and alternative stimulation and in disease conditions where the inner-ear impedances are changed, such as superior semicircular canal dehiscence (SCD). We employ this technique to answer questions that could not be previously addressed: Aim 1) Evaluate and improve methods for stimulating the RW. RW stimulation with crudely-modified middle-ear implants has aided numerous patients with CHL that were not helped by other means. However, hearing results have varied. We will develop a coupling system for RW stimulation that is specific for the unique anatomy and mechanical properties of the RW. This system will provide safer, more efficient and consistent RW stimulation. By measuring DP in the controlled environment of human cadaveric preparations, the performance of our coupling system will be compared quantitatively to other RW stimulation coupling methods, and critical features for safety, efficiency, consistency and ease of surgical implementation will be ascertained. Furthermore, the mechanical specifications required to optimize performance of a RW actuator will be determined. Aim 2) Elucidate the mechanisms involved in BC stimulation of the ear and determine how BC is affected by different pathologies. BC stimulation is used to diagnose sensory-neural hearing loss and to treat conductive and mixed hearing loss, yet the mechanisms of BC stimulation are not well understood. We will advance the understanding of BC and its effects by measuring intracochlear differential pressure, DP, evoked by BC stimulation in human cadaveric preparations. The study will: 1) Determine the contributions to BC of the inertial effects of ossicular motion and cochlear fluids and the compression effect of surrounding bone; 2) Determine the effects of the direction of BC stimulation; and 3) Determine the effect of SCD on BC. The measurements of BC-evoked DP will elucidate BC mechanisms and improve applications of BC for diagnosis and treatment.